Researchers turn attention to breast cancer prevention

Cheryl Corbin

Barbara Haddock Taylor, Baltimore Sun

Cheryl Corbin had her breasts removed after testing positive for the inherited gene mutation linked to the disease. She said she would gladly have taken a pill if it would have reduced her odds of developing breast cancer as much as surgery.

Cheryl Corbin had her breasts removed after testing positive for the inherited gene mutation linked to the disease. She said she would gladly have taken a pill if it would have reduced her odds of developing breast cancer as much as surgery. (Barbara Haddock Taylor, Baltimore Sun)

Cheryl Corbin's mother and grandmother had breast cancer, so an oncologist suggested she be tested for an inherited gene mutation linked to the disease. But when the results came in, she didn't show up to hear them.

"I was afraid to hear the words," Corbin, 47, said. "There's no turning back from there."

A genetic counselor tracked her down at the University of Maryland Women's Health clinic, where she is an office manager, and told her that she had the mutation that gave her an 85 percent chance of developing breast cancer. Corbin had no doubt about her next move — she had her breasts removed.

Such wrenching decisions are made by many women at high risk for breast cancer because it's the mosteffective way to prevent the disease that strikes one in eight women.

But now scientists, dissatisfied with the choices, are advancing other possible preventive treatments to reduce the odds of getting breast cancer.

In laboratories across Baltimore and around the nation, the scientists are testing drugs for prevention. They are also exploring chemical compounds found in broccoli, soy and fat, among others, that may also significantly reduce the risk of side effects of those drugs.

"Prevention is obviously the way to go now," said Angela Brodie, a University of Maryland researcher who helped pioneer a now common set of breast cancer treatment drugs called aromatase inhibitors. "And there's been some significant progress. Step-by-step progress."

A decade ago, Corbin and other patients often only had regular checkups and mastectomy as options for prevention.

More recently, doctors have turned to the drug tamoxifen for prevention. It blocks the effect of estrogen that fuels cancer and lowers risk of getting breast cancer by about 50 percent. But also can cause blood clots and endometrial cancer.

Raloxifene, an osteoporosis drug, also has been added to the prevention toolbox because it also has anti-estrogen effects. Studies have shown it may be slightly less effective than tamoxifen but also a bit less toxic.

Getting the most buzz now are newer versions of Brodie's aromatase inhibitors, widely used for treatment since the 1990s but shown in a study published in June to lower the risk of breast cancer in post-menopausal women by 65 percent.

The aromatase inhibitors are not yet approved by the U.S. Food and Drug Administration for prevention, but Brodie is optimistic. She said they treat breast cancer — and could thwart the disease — by blocking the action of the protein aromatase that helps produce estrogen made in the body after a post-menopausal woman's ovaries stop making the hormone.

She said her research began because she wanted to spare women radical surgery. Now the professor of pharmacology and experimental therapeutics at the University of Maryland's School of Medicine, who was not involved in the latest study, said she is hopeful the drug could not only improve survival rates but perhaps even ensure that women don't ever get the disease.

"That hasn't turned out to be such an easy task," she said. "But we're making progress."

State data from 2006 show the number of new cases of breast cancer annually were about 113 per 100,000 women, and mortality rates were about 25 per 100,000 women, just above the national average.

Taking up the mantle of preventing cancer is a new state task force, the Maryland State Council on Cancer Control, led by Dr. Kathy J. Helzlsouer, director of the Prevention and Research Center at Mercy Medical Center.

She said new preventive drugs are needed because those on the market have such serious side effects. The aromatase inhibitors can cause osteoporosis. She noted a study coordinated by the University of California, San Francisco, which found women were more likely to die after a hip fracture than from breast cancer.

Helzlsouer said there is no one good preventivestep for breast cancer, like quitting smoking to reduce lung cancer risk. A balanced diet, for example, is necessary for good health, but there appears only to be a link between obesity and breast cancer in post-menopausal women.

She did say a woman's risk is connected to how early she had her first period (later lowers risk) and first child (later raises risk). Alcohol, exposure to radiation from X-rays and a family history also pose levels of risk. They are considered on the Gail model, a risk assessment tool developed at the National Cancer Institute.

Helzlsouer said the first step is to know where a woman is on the spectrum. Those with high risk might consider genetic testing like Corbin and drugs best suited to them or a mastectomy.

"There are advances in field so we can better tailor treatment," she said. "In early '80s, a lumpectomy was a great advance. Now we're looking for the next great advances and more personalized medicine."

Personalized medicine means tailoring treatments to a person's specific genetic makeup, but there is limited knowledge so far for breast cancer. But some researchers are taking it a step beyond the search for gene mutations.

Dr. Kala Visvanathan, an associate professor in oncology and epidemiology at Johns Hopkins, is among those looking for other biological markers that could better predict risk for breast cancer. Once new markers are identified, they can also serve as specific targets for therapy.

Now women, particularly those at moderate risk, are less willing to start preventive medications and opt for regular screenings — indeed some of Corbin's family members have eschewed genetic testing and surgery.

"People don't want to take a risk with a pill with side effects if they don't have to," Visvanathan said. "And if they can avoid surgery, even better."

Researchers including Visvanathan also are looking into other therapies that aren't so toxic or invasive. One area of her focus is the sulforaphane in broccoli sprouts. The chemical compound has been shown to prevent breast cancer in animal models, and it can potentially be incorporated into the diet as a food or as a supplement from an early age. The preventive quality could translate to all kinds of breast cancer, including the small subset that doesn't respond to anti-estrogen therapies tamoxifen and aromatase inhibitors.

Visvanathan is looking at sulforaphane's ability to induce protective enzymes in the breast and stop cancer cells from proliferating. In one early study that showed the compound would reach the breasts, women who were scheduled to have breast reduction were given broccoli sprout extract with sulforaphane a half hour before surgery. Another ongoing study in women with cancer is measuring what happens to the sulforaphane once it's in the tissue, urine and blood. And another study is evaluating the impacts on cancer-free women.

"What's impressive about all these drugs [such as tamoxifen and aromatase inhibitors] is they have been used to successfully prevent breast cancer, at least in the short term," she said. "Now we want to fine tune — optimize benefits and minimize side effects so more women at risk will consider such preventive strategies."

There is more fine-tuning going on across the country, and on Hopkins' campus. There, researchers are looking at a hormone from fat tissue called leptin, soy and even older chemotherapy drugs. Dr. Vered Stearns, co-director of the Breast Cancer Program at Hopkins, is looking at the chemo drug Doxil.

In a small sample of women who were about to have mastectomies, Stearns delivered the drug through tiny catheters into the network of ducts that deliver milk to the nipple because this is where breast cancer often develops. If it kills cancer cells, women could prevent disease with treatment once every two to five years or longer.

Doses would be far lower than for traditional chemo treatments and would have less harsh side effects, and the drug would also prevent all types of breast cancer. Stearns is now experimenting with different drugs, including ones more natural than the chemo drug that may be palatable to more women. She's also trying to determine the proper dosage and how long the effects may last.

"I'm very optimistic we may have many different approaches in future," she said. "The challenge is how to implement them and make them attractive and disseminate that. Now we see only women at very high risk, but we're interested in the next step, something acceptable to more women and their physicians."

As for Corbin, she said she would gladly have taken a pill if it would have reduced her odds of developing breast cancer as much as surgery. But for now, she said she made the right choice — a pathology report from her breast tissue showed cancer cells were already forming, and she dodged certain disease within three years.

She wants her daughter, now in her 20s, to have better options in coming years.

"And I have brand new granddaughter, and hope she never has to worry about anything like this at all."

An earlier version misspelled Dr. Vered Stearns' name. The Sun regrets the error.

Drugs on the market: Tamoxifen and raloxifene, a breast cancer treatment and an osteoporosis drug, block the estrogen tumors use to grow. They reduce risk by 50 percent or less and can have side effects such as blood clots and other kinds of cancer.

Promising studies: Aromatase inhibitors, also used to treat breast cancer, were recently shown in a study to reduce risk by 65 percent in post-menopausal women, but they can cause osteoporosis.

Breast cancer prevention

The gold standard to reduce risk is a mastectomy. Only women at very high risk generally consider this surgery. But there are approved alternatives and others in the works:

In the pipeline: Studies on the chemical compound sulforaphane found in broccoli sprouts, a hormone from fat tissue called leptin, soy and small doses of older chemotherapy drugs are all being explored as less toxic preventive measures, among others.

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